Pediatric Palliative Care

An Inpatient Oncology Perspective

HPC Palliative Spring Education Event March 23, 2017 Paula MacDonald, RPh, Pediatric Oncology

Objectives

Present palliative pediatric oncology cases that illustrate symptoms such as • pain • cytopenias • bleeding • nausea/vomiting • constipation • dyspnea • secretions

Objectives

Review medications and tools used for pediatric symptom management

Highlight challenges to provision of

care in children Provide some “practical pearls” to

enhance provision of palliative care to pediatric patients

GOAL

To demonstrate that strategies for palliative symptom management in pediatric patients are not that different than those used for adult palliative patients.

Introduction Symptom management for children

with end-stage cancer presents a challenge to health care providers

Interdisciplinary family-centered care is an integral part of the symptom management for these children

n = 473

T. Dangel (Poland) R. Drake (Australia)

A. Goldman (UK) T. Hongo (Japan)

J. Wolfe (USA)

Pain 84 %

Fatigue 63 %

Nausea/Vomiting 58 %

Dyspnea 55 %

Constipation 47 %

Pediatric symptoms during last week of life

CASE: 12 yr ♀ metastatic NBL Long-standing recurrent/refractory NBL

• Extensive progression of bony disease • Large cranial lesion with intracranial

extensions • No possibility of cure

Severe pain in legs, back, head, etc.

Overarching goal of care: Go home as much as possible for as

long as possible!!!!

June Dec

CASE: 12 yr ♀ metastatic NBL Initial goal at disease progression: optimize pain control as outpatient as long as possible

initially requested no central IV access but

agreed to oral medications and radiation

Chemotherapy (irinotecan + temozolomide) stopped after 2 cycles due to prolonged neutropenia, thrombocytopenia and diarrhea

CASE: 12 yr ♀ metastatic NBL

So… what to do about her pain? oral hydromorphone PRN initially (≠ morphine, acetaminophen, NSAIDs)

1. Radiate skull, R hip and back lesions

2. REGULAR hydromorph contin + bolus: 9mg PO q12h + 2mg q2h PRN

When pain worsened, increased to 12mg PO q12h + 3mg breakthrough q2h PRN

Challenges Tolerance vs rapid disease progression Morphine allergy Lorazepam intolerance (agitation) Thrombocytopenia (≠ NSAIDs) No fentanyl infusions outside PICU No authorized methadone prescriber in

community

Myths Related to Pain and Pain Management in Children

Risk of respiratory depression Addiction Child that is sleeping or playing does not

have pain Presence of pain indicates worsening of

disease or approaching death

WHO Guidelines on the pharmacological treatment of persisting pain in children (2012)

Dosing at regular intervals: • Around the Clock

Adapting treatment to the individual child: • With the Child

Using the appropriate route of administration: • By the appropriate route

Using a two-step strategy: • By the Analgesic Ladder

Assessment

Using the appropriate route of administration (i.e. Least traumatic)

Use oral/enteral route, when possible Alternative routes:

• Sublingual/buccal • Intranasal • Transdermal (contraindicated in acute pain) • Rectal • Intravenous (or subcutaneous) • Intramuscular = obsolete

Using a two-step strategy

WHO Step 1 Mild Pain

WHO Step 2 Moderate to Severe Pain

Ibuprofen and/or

Acetaminophen

Other NSAIDs? Cox-2 Inhibitor?

Morphine

or Fentanyl,

Hydromorphone, Methadone

OTC Analgesics Acetaminophen

• may mask fever and infection in neutropenia • 10-15 mg/kg/dose; repeat every 4-6 hrs • Oral, rectal

NSAIDs • Anti-inflammatory; good for bone pain • Caution: with thrombocytopenia, renal dysfxn • Ibuprofen 5-10 mg/kg PO every 6-8 hrs • Ketorolac 0.5 mg/kg IV every 6-8 hrs • Naproxen 5-10 mg/kg PO/PR q8-12h (max 20

mg/kg/d) ** Rectal administration is contraindicated in neutropenic and thrombocytopenic patients

Opioid drug options Phenanthrene derivatives

• Morphine: Gold Standard • Hydromorphone • Oxycodone (not recommended) • Codeine (not recommended)

Phenylpiperidine derivatives • Fentanyl

Diphenylheptane derivatives • Methadone

Intranasal Fentanyl Rapid and effective minimization of pain Indicated for Moderate to Severe Acute

Pain when IV access not available or necessary

Contraindicated if allergy to fentanyl or other opiates, altered conscious state, occluded nasal passages, intubated pts, URTI with nasal secretions, epistaxis

Intranasal Fentanyl Dose: 1.5 mcg/kg/dose Repeat q5mins, PRN Onset: 2-5 minutes Duration: ~ 30 minutes to 2 hours Administration via Mucosal Atomization

Device (MAD):

Tool kits at www.caphc.org

Intranasal Fentanyl Adverse Effects

• Bitter taste • Nasal irritation • Respiratory depression • Dyspnea/cough • Hypotension • Excessive sedation • Pruritus • Chest wall rigidity (with large doses) Monitoring same as with IV opioids

HHSC Opioid Equivalencies

Drug Parenteral (mg) PO (mg)

FentaNYL 0.1 N/A

HYDROmorphone 2 4-6

Morphine 10 20-30

OxyCODONE N/A 10-15

Methadone N/A 2.5-10

Opioid Rotation

Morphine is gold standard first line • BUT, it is not always best for every child

≥10% of children have inadequate pain control with intolerable side effects • May respond to opioid rotation! • If in renal failure consider: fentanyl, methadone • Premature infants: fentanyl • Equianalgesic dosing

Side effects

Analgesia

What about neuropathic pain? Multiple causes of neuropathic pain

in childhood cancer: Tumor infiltration (nerve compression) Phantom limb pain Spinal cord compression ↑ intracranial pressure Neuropathy (e.g. from chemotherapy) *Currently no validated neuropathic pain scales for children < 18 years of age.

What about neuropathic pain? Start with opioids Consider addition of adjuvant agents Tricyclic antidepressants*

– Amitriptyline, Nortriptyline – Side effects: sedation, anticholinergic effects,

prolonged QTc. Wean over 1 week

Gabapentinoids* – Gabapentin, pregabalin – Mechanism: calcium-channel blocker, decrease

release of pain transmitters – Side effects: nystagmus, thought disorder,

hallucinations, headache, and myalgia. Wean 1-2 wks

Pediatric doses of adjuvant agents Amitriptyline (or Nortriptyline) Dose same for both

– Starting dose: 0.1 mg/kg po qhs – Slowly titrate up to 1 mg/kg/day (usually 5-10 mg to start, then max 50-75 mg/day)

Gabapentin – Starting dose: 5-10 mg/kg/dose (max 100 mg/dose);

start QHS, then BID, then TID-QID – Titrate by 5 mg/kg/day every 3-4 days based on

response (max 50 mg/kg/day OR 3600 mg/day) – May titrate more rapidly for severe pain

Adjuvant agents

NMDA receptor channel blockers: – Ketamine (low-dose infusion)

– Dissociative anesthetic, analgesic at low doses – Side effects: intracranial hypertension, tachycardia,

psychomimetic phenomena (give lorazepam) – 1-2 mcg/kg/min IV continuous infusion

– Methadone – Mu-opioid receptor agonist and NMDA receptor

antagonist – Also serotonin and norepinephrine reuptake

inhibitor

CASE: 12 yr ♀ metastatic NBL

Her pain worsens – PO not fast enough: 1. Switch to hydromorphone IV (CADD):

– 8mcg/kg/hr plus boluses 4mcg/kg – Titrate increases: by 50% of dose – Her max reached: 620mcg/kg/hr!!!! (gradual increase

over months; good efficacy; manageable side effects)

2. Amitriptyline added: 10mg PO qhs

3. Ketorolac added: 10mg q6h IV

4. Methadone added: – Started 0.5mg PO BID 2mg PO TID

CASE: 12 yr ♀ metastatic NBL

Other symptoms:

Cytopenias; bleeding risk Anxiety/ OCD-like behaviour Anorexia/Cachexia/Dehydration Nausea/Vomiting Constipation

Cytopenias Caused by:

• Decreased production (chemo, radiation, bone marrow infiltration of malignant cells)

• Destruction, Sequestration Management: (symptom focused!) * Reduce risks (i.e. no rectal meds, ↓ invasive procedures)

• Anemia – fatigue, respiratory compromise - PRBCs • Neutropenia – infection risk – antibiotics/ G-CSF • Thrombocytopenia – transfuse; no NSAIDs

Bleeding and hemorrhage Caused by:

• Thrombocytopenia (e.g. nosebleeds) • Liver dysfunction (e.g. altered clotting mechanism) • Tumour invasion (e.g. lungs – hemoptysis, GI)

Management:

*

Dark-colored towels and bed linens readily available

Small Bleed (localized) Platelet transfusions, pressure/packing, hemostatic dressing (thrombin, gelfoam), gauze + tranexamic acid, cautherization

Heavy Bleed (systemic) Tranexamic acid IV (10 mg/kg q8h), vitamin K, pantoprazole, octreotide, PRBCs, platelet transfusions, FFP, IV fluids if hypotensive

Acute Catastrophic Bleed Sedation (e.g. IV/SC or intranasal midazolam, sublingual lorazepam)

Anxiety Child life involvement Emotional-expressive play therapy Benzodiazepines:

• Treatment of choice in children • Antiemetic properties • Sleep initiation – caution oversedation • Short-acting: lorazepam 0.02-0.05 mg/kg q6-8h

PO/SL/IV/Subcut

• Longer acting: clonazepam BID or TID dosing; better anticonvulsant

BUT: paradoxical agitation (40% children)

OCD-like Behaviours Second-generation neuroleptics

• e.g. Risperidone, Olanzapine • First line in children and adolescents • ↓ EPS, dystonia, tardive dyskinesia • Start low dose; titrate up slowly

Risperidone: start 0.25-0.5 mg qhs; ↑ bid or tid Olanzapine: (Zydis) start 2.5 – 5 mg qhs

• Quick dissolve dosage forms • ** weight gain, ↑ appetite • ↓ seizure threshold

Anorexia-Cachexia Anorexia: loss of appetite, decreased food intake

• Loss of taste, pain, constipation, N/V, anxiety, depression

Cachexia: involuntary weight loss, lack of nutrition

• Limited ability to eat, chew or swallow, metabolic abnormalities

Anorexia-Cachexia Goal of Care: ↑ appetite → promote wt gain ** slow rate of weight loss **

• favourite high-calorie foods, soft foods • Nutritional supplementation – enteral vs parenteral • Appetite stimulants (e.g. Cyproheptadine, steroids) • Treat underlying causes of ↓ appetite: - constipation - N/V - pain - anxiety - thrush

Dehydration excessive loss of water

• limited ability to consume sufficient fluids • increased losses

Hydration intervention – controversial; individualized • Goal: ↓ thirst for comfort help maintain renal function • Caution: peripheral edema • ≠ evidence that hydration ↑ terminal secretions

Goals of Nutrition and Fluid Management in the Dying Child

Alleviate any hunger and thirst

Reduce anxiety about intake

Preserve the social aspects of mealtimes

Constipation Causes:

• Disease-related (e.g. obstruction, neurologic, hypercalcemia, inactivity)

• Treatment-related (e.g. opioids, vincristine)

• Change in diet Management:

• Diet (high fiber) and fluids • Activity • Toileting • Medications

Medications to treat Constipation Osmotic – PEG 3350, lactulose, Citromag

Bulk forming (fibre) - Metamucil Stimulants – senna, bisacodyl, PicoSalax

Stool softeners - docusate Lubricants - mineral oil, glycerine Opioid reversal - methylnaltrexone Motility agents – domperidone, metoclopramide

Caution: thrombocytopenia, neutropenia, obstruction

Nausea and Vomiting Causes

• GI – infection, obstruction, ileus, constipation • Metabolic – hypoglycemia, electrolyte imbalance • CNS - ↑ ICP, anxiety; brain tumour location • Treatment – opioids, chemo, radiation

Management

• Distraction • Dietary • Small meals + slow feeding • Medications

Antiemetics Drug Class Dosing SEs

5-HT3 Antagonists Ondansetron 0.15 mg/kg tid IV/PO/SL/SC Granisetron 20-40 mcg/kg bid IV/PO

Constipation, HAs, prolongation of QT interval

H1 Antagonists Dimenhydrinate 0.5-1 mg/kg q4-6h IV/PO/PR

Drowsiness, dry mouth

Dopamine Antagonists Prochlorperazine 0.1 mg/kg q6h PO Chlorpromazine 0.5 mg/kg q6h IV/PO/PR

Limited use in pediatrics due to EPS; sedation, hypotension *with diphenhydramine

Prokinetics Domperidone 0.3-0.6 mg/kg tid or qid PO only Metoclopramide 0.1-0.2 mg/kg IV/PO q6h

Max 30 mg/day due to QT prolongation (Health Canada warning) Contraindicated < 1 y.o. *with diphenhydramine

Antiemetics Drug Class Dosing Ses

Cannabinoids Nabilone 0.5-2 mg bid to tid PO (for pts > 18 kg)

Drowsiness, hallucinations, dysphoria, dry mouth, tachycardia

Corticosteroids Dexamethasone 0.1-0.25 mg/kg bid-qid IV/PO/SC (maximum 8 mg /dose)

Mood/behaviour changes, increased appetite, edema, give with antacid

Benzodiazepines Lorazepam 0.025-0.1 mg/kg bid-qid IV/PO/SL (maximum 2 mg/ dose)

* For anticipatory N/V Sedation

Antipsychotics Haloperidol 0.01-0.1 mg/kg bid-tid PO/IV Olanzapine 2.5-5 mg PO once daily (regular and ODT available)

*limited due to EPS ; reserved for refractory cases Limited evidence pediatric antiemetic dosing; reserved for refractory cases

Case: 16 yr ♂ – High-grade brain stem glioma

Diagnosed with DIPG • High grade brain stem glioma • 10-20% of childhood brain tumours • Very aggressive, poor prognosis • No surgical removal; no chemotherapy • Radiation = temporary response (~ 6-9 months) • Post radiation inflammation = Radiation Necrosis • Dexamethasone for symptom control

Case: 16 yr ♂ – High-grade brain stem glioma

Palliative care initiated in community

episode of coughing, difficulty swallowing → Panic Attack → Admit • Unable to stand, walk or speak • Extreme hunger (dexamethasone) but

coughing with liquids, secretions • Tongue numbness • Dyspnea

Case: 16 yr ♂ – High-grade brain stem glioma Overarching goal of care:

• Comfort, surrounded by loved ones • End-of-life in hospital

• Issues: – Hunger : NG tube + feeds for satiety – Communication: IPAD + eye movements – Restlessness: lorazepam sublingually – Secretions: scopolamine (Intima – SC) – Dyspnea: O2 by nasal prongs – Legacy-building: organ donation

Secretions ↓ ability to swallow and clear oral secretions

Contributing factors: • Pulmonary malignancy • Pulmonary edema • Dysphagia • Generalized weakness • Altered consciousness

Interventions: • Humidified air • Suctioning (may ↑ secretions) • Medications

Management of Terminal Secretions Drug Dose Comments

Scopolamine (Hyoscine hydrobromide)

0.4-0.6 mg OR 5-10 mcg/kg IV/SC q4-8h (maximum dose 0.6 mg)

• Sedating • May cause delirium • Dry mouth

Transderm-V Patch (Scopolamine) – 1.5 mg

2-3 yrs: ¼ patch 3-9 yrs: ½ patch 10+ yrs: 1 patch

• Q72hrs • Sedating, delirium • Place behind ear

Glycopyrrolate PO: 40-100mcg/kg q6-8h IV/SC: 4-10 mcg/kg q3-4h (maximum 200 mcg/dose)

• Less sedating and

less effective than scopolamine

Dyspnea = distressing SOB; breathlessness Causes in cancer patients: Respiratory

• Metastatic lung disease - obstruction • Pleural effusion, pulmonary edema, ascites • Pulmonary embolism • Pneumonia

Cardiac • CHF, superior vena cava obstruction, anemia

Treatment related • Radiation pneumonitis, chemotherapy induced

cardiomyopathy or pulmonary fibrosis

Assessment of Dyspnea Dyspnea Scales

Treatment of Dyspnea

Non-pharmacological: • Oxygen • Fan, open window • Sit upright • Calm reassurance • Relaxation and distraction • Cool temperature • Humidifier • Pursed-lip breathing exercises

Treatment of Dyspnea Pharmacological:

• *Opioids* – treatment of choice! Low dose morphine (30-50% pain dose) Already on opioid – titrate dose up to effect

• Benzodiazepines - adjunct Lorazepam – for anxiety/panic with dyspnea

0.05-1 mg/kg/dose q6-24h Midazolam – infusion for acute resp distress

1-5 mcg/kg/min – titrate to effect Children require higher doses

Disease-specific Medications for Dyspnea

• Diuretics (e.g. furosemide) – CHF, ascites • Corticosteroids – obstruction, pneumonitis • Antibiotics – pneumonia

• Anticoagulants - pulmonary embolism

• Transfusion – anemia

• Chemotherapy/radiation – metastases

Treat underlying cause!

Pediatric Pearls Multidisciplinary – “it takes a village”

Define overall goals of care – patient & family

Adapt treatment to individual child

Child that is sleeping, playing or quiet can still have pain

Rotate opioids if ineffective or intolerable SEs

Use consistent pain assessment scales

Children with cancer can require extremely high doses of opioids at end of life (e.g. solid tumours, NBL)

Pediatric Pearls Alternative routes of administration are safe and

effective (e.g. intranasal, subcutaneous, SL) – insuflons, Intima devices, MAD, CADD pumps

Opioids = drugs of choice for pain, dyspnea but Ø codeine or meperidine in children

Topical tranexamic acid ↓ localized bleeding

Caution with chlorpromazine, haloperidol, metoclopramide and prochlorperazine in children due to ↑ risk of EPS, dystonias, tardive dyskinesia

(give with IV diphenhydramine if benefits > risk)

Inpatient End-of-Life Care Advantages:

• Access to multidisciplinary team & specialists • Quick access to IV blood products, IV medications, cardioresp

monitors • Emotional support from staff, other parents • Medical personnel close for emergencies (ICU)

Disadvantages: • Not home-like environment • Limited room for family and friends • Medical, sterile • Lack of quiet and privacy • Medical learners on weekends/evenings – inexperienced • Difficult to transition from “active treatment” to “comfort care”

Goals for the Future

Continue to develop a collaborative relationship between McMaster Children’s Hospital and our colleagues in the community so that we can create more opportunities for our pediatric oncology patients to receive end-of-life care in their home communities.

Questions? Comments?

Thank you!